Poseltinib
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MedKoo CAT#: 327020

CAS#: 1353552-97-2

Description: Poseltinib, also known HM-71224 and LY3337641, is a tyrosine kinase inhibitor. Poseltinib is an experimental Bruton's tyrosine kinase inhibitor for the treatment of rheumatoid arthritis. HM71224 irreversibly bound to and inhibited Btk (IC50 = 1.95 nM). The compound also inhibited the phosphorylation of Btk and its downstream molecules such as PLCγ2, in activated Ramos B lymphoma cells and primary human B cells in a dose-dependent manner. Furthermore, HM71224 effectively inhibited the production of tumor necrosis factor (TNF)-α, interleukin (IL)-6, and IL-1β by human monocytes, and osteoclast formation by human monocytes. HM71224 inhibits Btk in B cells and monocytes and ameliorates experimental arthritis in a mouse model. HM71224 is a potential novel therapeutic agent for rheumatoid arthritis in humans.


Chemical Structure

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Poseltinib
CAS# 1353552-97-2

Theoretical Analysis

MedKoo Cat#: 327020
Name: Poseltinib
CAS#: 1353552-97-2
Chemical Formula: C26H26N6O3
Exact Mass: 470.21
Molecular Weight: 470.530
Elemental Analysis: C, 66.37; H, 5.57; N, 17.86; O, 10.20

Price and Availability

Size Price Availability Quantity
10mg USD 90 Ready to ship
25mg USD 190 Ready to ship
50mg USD 350 Ready to ship
100mg USD 550 Ready to ship
200mg USD 950 Ready to ship
500mg USD 1950 Ready to ship
1g USD 2950 Ready to ship
2g USD 5250 Ready to ship
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Synonym: Poseltinib; HM 71224; HM-71224; HM71224; LY 3337641; LY3337641; LY-3337641

IUPAC/Chemical Name: N-(3-((2-((4-(4-methylpiperazin-1-yl)phenyl)amino)furo[3,2-d]pyrimidin-4-yl)oxy)phenyl)acrylamide

InChi Key: LZMJNVRJMFMYQS-UHFFFAOYSA-N

InChi Code: InChI=1S/C26H26N6O3/c1-3-23(33)27-19-5-4-6-21(17-19)35-25-24-22(11-16-34-24)29-26(30-25)28-18-7-9-20(10-8-18)32-14-12-31(2)13-15-32/h3-11,16-17H,1,12-15H2,2H3,(H,27,33)(H,28,29,30)

SMILES Code: C=CC(NC1=CC=CC(OC2=C(OC=C3)C3=NC(NC4=CC=C(N5CCN(C)CC5)C=C4)=N2)=C1)=O

Appearance: Solid powder

Purity: >98% (or refer to the Certificate of Analysis)

Shipping Condition: Shipped under ambient temperature as non-hazardous chemical. This product is stable enough for a few weeks during ordinary shipping and time spent in Customs.

Storage Condition: Dry, dark and at 0 - 4 C for short term (days to weeks) or -20 C for long term (months to years).

Solubility: Soluble in DMSO

Shelf Life: >2 years if stored properly

Drug Formulation: This drug may be formulated in DMSO

Stock Solution Storage: 0 - 4 C for short term (days to weeks), or -20 C for long term (months).

HS Tariff Code: 2934.99.9001

More Info:

Biological target: Poseltinib is a Bruton’s tyrosine kinase (BTK) inhibitor with IC50 =1.95 nM.
In vitro activity: To characterize the inhibitory effect of HM71224 on the BCR signaling pathway, the activation of BTK and PLCγ2, the physiological substrate of BTK, following stimulation with anti-IgM was examined in human Ramos B lymphoma cells. HM71224 blocked both autophosphorylation of BTK and phosphorylation of PLCγ2 with IC50 values of less than 10 nM (Fig. 1a). To explore the inhibitory effect of HM71224 on the FcγR signaling cascade, the production of the inflammatory cytokines TNF-α and IL-6 was evaluated following stimulation with anti-IgG in human monocyte THP-1 cells. Production of both TNF-α and IL-6 effectively decreased in a dose-dependent manner (Fig. 1b and c). Reference: Arthritis Res Ther. 2017 Sep 26;19(1):211. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5615432/
In vivo activity: HM71224 had therapeutic effects related to the amelioration of kidney damage caused by lupus-like renal inflammation. Intrarenal B cells can contribute to renal damage and inflammation by enhancing the immunological response as antigen-presenting cells, inducing cytokine-promoting T cell proliferation and lymphatic angiogenesis, and enhancing the local immune response to persisting autoantigens in the tubulointerstitium. In both MRL/lpr and NZB/W F1 mice, activation of TLR9 caused accelerated LN. On the other hand, LN develops via unique mechanisms in each strain like the highly heterogenous nature of SLE. NZB/W F1 mice promote the renal damages B cell dependent manner including secretion of autoantibody, whereas MRL/lpr mice develop the renal damages via antigen presentation and cytokine production by B cells, not secretion of autoantibodies. HM71224 markedly reduced splenic B cell numbers, including those of germinal center B cells, plasma B cells, and activated B cells. HM71224 also had inhibiroty effects on BCR and FcR signaling. These mechanisms of action of HM71224 might lead to significant amelioration of renal injury and lymphocyte infiltration in both animal models, although differences in strains in the pathogenesis of LN can lead to different degrees of therapeutic drug efficacy. It is possible that the therapeutic effects of HM71224 in glomerulonephritis, interstitial nephritis, and vessel inflammation in murine LN were mediated by B cell inhibition. Reference: Arthritis Res Ther. 2017 Sep 26;19(1):211. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5615432/

Solubility Data

Solvent Max Conc. mg/mL Max Conc. mM
Solubility
DMSO 100.0 212.53

Preparing Stock Solutions

The following data is based on the product molecular weight 470.53 Batch specific molecular weights may vary from batch to batch due to the degree of hydration, which will affect the solvent volumes required to prepare stock solutions.

Recalculate based on batch purity %
Concentration / Solvent Volume / Mass 1 mg 5 mg 10 mg
1 mM 1.15 mL 5.76 mL 11.51 mL
5 mM 0.23 mL 1.15 mL 2.3 mL
10 mM 0.12 mL 0.58 mL 1.15 mL
50 mM 0.02 mL 0.12 mL 0.23 mL
Formulation protocol: 1. Kim YY, Park KT, Jang SY, Lee KH, Byun JY, Suh KH, Lee YM, Kim YH, Hwang KW. HM71224, a selective Bruton's tyrosine kinase inhibitor, attenuates the development of murine lupus. Arthritis Res Ther. 2017 Sep 26;19(1):211. doi: 10.1186/s13075-017-1402-1. PMID: 28950886; PMCID: PMC5615432.
In vitro protocol: 1. Kim YY, Park KT, Jang SY, Lee KH, Byun JY, Suh KH, Lee YM, Kim YH, Hwang KW. HM71224, a selective Bruton's tyrosine kinase inhibitor, attenuates the development of murine lupus. Arthritis Res Ther. 2017 Sep 26;19(1):211. doi: 10.1186/s13075-017-1402-1. PMID: 28950886; PMCID: PMC5615432.
In vivo protocol: 1. Kim YY, Park KT, Jang SY, Lee KH, Byun JY, Suh KH, Lee YM, Kim YH, Hwang KW. HM71224, a selective Bruton's tyrosine kinase inhibitor, attenuates the development of murine lupus. Arthritis Res Ther. 2017 Sep 26;19(1):211. doi: 10.1186/s13075-017-1402-1. PMID: 28950886; PMCID: PMC5615432.

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1: Park JK, Byun JY, Park JA, Kim YY, Lee YJ, Oh JI, Jang SY, Kim YH, Song YW,
Son J, Suh KH, Lee YM, Lee EB. HM71224, a novel Bruton's tyrosine kinase
inhibitor, suppresses B cell and monocyte activation and ameliorates arthritis in
a mouse model: a potential drug for rheumatoid arthritis. Arthritis Res Ther.
2016 Apr 18;18:91. doi: 10.1186/s13075-016-0988-z. PubMed PMID: 27090981; PubMed
Central PMCID: PMC4835877.